Phase I trial of thalidomide and capecitabine for treatment of metastatic colorectal cancer
| Autor: | M. J. Goldstein, A. Chapman, K. Sharan, J. C. Leighton, A. Muskett, J. Sansom, Edith P. Mitchell |
|---|---|
| Rok vydání: | 2006 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 24:13552-13552 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2006.24.18_suppl.13552 |
| Popis: | 13552 Background: Survival of patients with metastatic colorectal cancer (CRC) has increased with the advent of new chemotherapeutic and biologic agents. Yet, there remains a need for more effective third- and fourth-line chemotherapy. Thalidomide (Thal) has angiogenic and immunomodulatory properties and antitumor effects have been consistently demonstrated in pts with multiple myeloma and occasionally in pts with advance solid tumors. Capecitabine (Cape) has demonstrated efficacy as a single agent and in combination therapy in pts with metastatic CRC. We conducted a phase I study of Thal/Cape in pts with refractory metastatic CRC previously treated with irinotecan, oxaliplatin and fluoropyrimidines. Methods: Pts with metastatic CRC who had received two or more prior chemotherapy regimens were eligible. Treatment consisted of Cape at 1500 mg/m2 po daily for 14 days every three weeks with dose levels increasing to 2500mg/m2; Thal dosing was initially 100 mg with escalations individually to 400 mg per day. Toxicity rates, response and overall survival were analyzed. Results: Twenty-five eligible pts were enrolled; median age= 58 (20–79); M/F=13/12; ECOG PS 0/1/2=11/12/2. The median number of Thal/Cape cycles administered was 3 (range 1–9). Treatment was well tolerated; grade 3–4 non-hematologic toxicities included somnolence/syncope (20%), fatigue (20%), constipation (10%), diarrhea (10%), infections (10%) and neuropathy, thrombosis, hypoglycemia, nausea/vomiting each occurred in 5% of pts; grade 3–4 hematological toxicities anemia (15%), neutropenia (5%), prolonged prothrombin time (15%), increased LFTs (10%). Grade 3–4 hand-foot syndrome occurred in 2 pt (8%). There were no radiographic responses, but 6 pts achieved a decline in CEA of 50% or greater and 6 pts achieved stable disease. Conclusion: The MTD is Cape 2500mg/m2 per day. The combination of Thal/Cape was well tolerated; the recommended dose is thal 200mg and cape 2000mg/m2. Despite the lack of radiographic responses, the rate and duration of disease stabilization observed in this heavily pretreated pt population suggest that this regimen may offer some benefit. [Table: see text] |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|